The most common adult brain cancers are metastases of cancers that arise elsewhere in the body and travel to the brain from other organs. These metastases are essentially incurable. More than 200,000 new cases occur in the United States each year and patients rarely survive one year. Breast cancer and lung cancer account for a majority of brain metastases. Therefore, new effective treatments for brain metastases from cancer are urgently needed.
The standard treatment of brain metastases is surgery or radiation. However, many tumors recur after surgery, radiation, and chemotherapy. A single brain metastasis can be managed by surgery or localized radiation. However, most patients harbor multiple small lesions. The blood–brain barrier prevents most cancer drugs from entering the brain and reaching effective concentrations, so there are no effective therapies that prolong life. The discovery of neural stem cells (NSCs) that home to areas of tumor in the brain offers an approach for new treatment.
Neural stem cells have been engineered to produce a protein that converts a harmless chemical into a toxic one that kills cells. These neural stem cells take the produced protein to the area of the brain where the tumors are located, and the protein converts the chemical into the toxin, which kills the tumor cells. This CIRM Disease Team Award will support an early phase clinical trial to test the safety of this approach in breast cancer patients with brain metastases that are growing following standard treatments.
Each year approximately 10,000 breast cancer patients with brain metastases will be diagnosed and many will die of complications of brain disease. Risk factors include certain types of breast cancer and young age. Neural stem cells offer a unique therapy that represents an extremely promising step forward to alleviate suffering in patients with disabling and life-threatening cancer complications.

Statement of Benefit to California:

Breast cancer and lung cancer account for a majority of patients with spread of cancer to the brain, called brain metastases. Approximately, 10,000 breast cancer patients in the United States have brain metastases annually and these patients typically live less than 12 months. Brain metastases often recur after standard surgery, radiation, and/or chemotherapy. Chemotherapy agents do not effectively penetrate the brain and no therapies that treat the entire body prolong survival.
Risk factors for brain metastases in breast cancer include young age and certain aggressive cancer types. New targeted therapies to certain types of breast cancer are effective at controlling breast cancer outside the brain but not in the brain. Other types of breast cancer are associated with brain metastases that progress at the same time as disease is progressing outside the brain. In both cases, patients frequently die of brain problems and new brain-directed therapies are urgently needed.
Neural stem cells offer promise for treatment of this deadly and disabling problem in breast cancer patients. Neural stem cells have been engineered to carry a tumor-killing gene and are attracted to cancer areas in the brain. The neural stem cells would perform this action without causing tumors or increasing growth of the patient's tumor. The neural stem cells carry cytosine deaminase, which converts a non-toxic chemical into a chemotherapy drug at that site of the tumor, killing the tumor. This treatment approach is currently being studied in patients with primary brain cancers.
In this proposal, we will evaluate the safety and the benefit of treating breast cancer patients with brain metastases that have returned after standard surgery or radiation by administering engineered neural stem cells. We plan to initiate clinical trial enrollment after we have performed all necessary animal safety testing and submitted a complete plan for review by the US Food and Drug Administration and the National Institutes of Health. Members of this team have experience in breast cancer, brain cancer, genetic biomarkers, clinical trials, imaging, and stem cell biology.
New and effective treatments for brain metastases are urgently needed. The strategy proposed in which neural stem cells are given to patients with brain metastases is supported by animal experiments, the current clinical studies in primary brain cancer, and the scientific expertise of our multidisciplinary team. Our proposed neural stem cell treatment for brain metastases represents a unique and extremely promising step forward to alleviate suffering in beast cancer patients with disabling and life-threatening cancer spread to the brain.
The citizens of California and their families afflicted by this disease may benefit from this promising new therapy. All California citizens will benefit from the national visibility accompanying a study of innovative therapy in a patient population with a huge unmet medical need.